Journal ArticleDOI
Expressions of PD-L1 and Nectin-4 in urothelial cancer patients treated with pembrolizumab.
H. Ueki,Nobuyuki Hinata,Koichi Kitagawa,Takuto Hara,Tomoaki Terakawa,Junya Furukawa,Ken-ichi Harada,Y. Nakano,M. Komatsu,Masato Fujisawa,Toshiro Shirakawa +10 more
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TLDR
In this article, the association between immunohistochemical biomarkers and clinical outcomes in urothelial cancer patients treated with pembrolizumab was explored and the associations between protein expressions and overall survival (OS), progression-free survival (PFS), and disease control rate (DCR) were statistically analyzed.Abstract:
Recently, the standard of care for advanced urothelial cancer (UC) has been changed by developing immune-checkpoint inhibitors (ICIs). However, its response rate is limited to 20–30%. The identification of biomarkers to predict the therapeutic effects of ICIs is urgently needed. The present study explored the association between immunohistochemical biomarkers and clinical outcomes in UC patients treated with pembrolizumab. A total of 85 patients with UC who received pembrolizumab after chemotherapy from January 2018 to May 2020 were retrospectively reviewed. Tumor tissues were obtained for immunohistochemical study from 47 out of 85 patients. The protein expressions of PD-L1, WT1, Nectin-4, CD4, CD8, Foxp3, and CD68 in tumor cells and/or tumor infiltrating lymphocytes were immunohistochemically examined. The associations between protein expressions and overall survival (OS), progression-free survival (PFS), and disease control rate (DCR) were statistically analyzed. Patients with positive PD-L1 in tumor cells showed significantly worse OS (Log-rank test: HR 5.146, p = 0.001, Cox regression analysis: HR 4.331, p = 0.014) and PFS (Log-rank test: HR 3.31. p = 0.022), along with significantly lower DCR (14.3%) compared to the PD-L1 negative patients (67.5%). In addition, patients with strong expression of Nectin-4 in tumor cells showed significantly higher DCR (100%) than the other patients (50%). PD-L1 expression in tumor cells was associated with poor prognosis (OS and PFS) and low DCR. Interestingly, the strong expression of Nectin-4 was correlated with high DCR. PD-L1 and Nectin-4 expression in tumor cells could be prognostic biomarkers useful for pembrolizumab in patients with advanced UC.read more
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Antibody-drug conjugates: beyond current approvals and potential future strategies
TL;DR: This review will summarise the clinical activity of ADCs in tumour types not covered elsewhere in this issue, such as gastrointestinal (GI) and genitourinary (GU) cancers and glioblastoma (GBM), and provide selected insights into future development of novel ADCs against new antigen targets in the tumour microenvironment (TME).
Journal ArticleDOI
Tumor expression of Nectin-1-4 and its clinical implication in muscle invasive bladder cancer: An intra-patient variability of Nectin-4 expression.
Makito Miyake,Tatsuki Miyamoto,Takuto Shimizu,Sayuri Ohnishi,Tomomi Fujii,Nobutaka Nishimura,Yuki Oda,Yosuke Morizawa,Shunta Hori,Daisuke Gotoh,Yasushi Nakai,Kazumasa Torimoto,Nobumichi Tanaka,Kiyohide Fujimoto +13 more
TL;DR: In this article , the authors evaluated expression of Nectins 1-4 in 64 patients with muscle invasive bladder cancer who underwent radical cystectomy using a histochemical scoring method (H-score; immunohistochemical staining intensity multiplied by the percentage of positive-staining cells).
Journal ArticleDOI
Antibody Drug Conjugates in Bladder Cancer: Current Milestones and Future Perspectives.
Journal ArticleDOI
Impact of Performance Status on Oncologic Outcomes in Patients with Advanced Urothelial Carcinoma Treated with Immune Checkpoint Inhibitor: A Systematic Review and Meta-analysis.
Tatsushi Kawada,Takafumi Yanagisawa,Hadi Mostafaei,Reza Sari Motlagh,Fahad Quhal,Pawel Rajwa,Ekaterina Laukhtina,M. von Deimling,Alberto Bianchi,Mohammed Majdoub,M. Pallauf,Benjamin Pradere,Jeremy Yuen-Chun Teoh,Pierre I. Karakiewicz,Motoo Araki,Shahrokh F. Shariat +15 more
TL;DR: In this article , the impact of patients' performance status on the oncologic outcomes in patients with advanced urothelial carcinoma (aUC) treated with ICIs was investigated.
References
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Journal ArticleDOI
Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: A single-arm, multicentre, phase 2 trial
Jonathan E. Rosenberg,Jean H. Hoffman-Censits,Thomas Powles,Michiel S. van der Heijden,Arjun Vasant Balar,Andrea Necchi,Nancy A. Dawson,Peter H. O'Donnell,Ani Balmanoukian,Yohann Loriot,Sandy Srinivas,Margitta Retz,Petros Grivas,Richard W. Joseph,Matthew D. Galsky,Mark D. Fleming,Daniel P. Petrylak,Jose Luis Perez-Gracia,Howard A. Burris,Daniel Castellano,Christina Canil,Joaquim Bellmunt,Dean F. Bajorin,Dorothee Nickles,Richard Bourgon,Garrett M. Frampton,Na Cui,Sanjeev Mariathasan,Oyewale O. Abidoye,Gregg Fine,Robert Dreicer +30 more
TL;DR: Treatment with atezolizumab resulted in a significantly improved RECIST v1.1 response rate, compared with a historical control overall response rate of 10%, and Exploratory analyses showed The Cancer Genome Atlas (TCGA) subtypes and mutation load to be independently predictive for response to atezolediazepine.
Journal ArticleDOI
Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma
Joaquim Bellmunt,Ronald de Wit,David J. Vaughn,Yves Fradet,Jae-Lyun Lee,Lawrence Fong,Nicholas J. Vogelzang,Miguel Angel Climent,Daniel P. Petrylak,Toni K. Choueiri,Andrea Necchi,Winald R. Gerritsen,Howard Gurney,David I. Quinn,Stéphane Culine,Cora N. Sternberg,Yabing Mai,Christian Heinrich Poehlein,Rodolfo F. Perini,Dean F. Bajorin +19 more
TL;DR: Pembrolizumab was associated with significantly longer overall survival and with a lower rate of treatment‐related adverse events than chemotherapy as second‐line therapy for platinum‐refractory advanced urothelial carcinoma.
Journal ArticleDOI
Association of PD-1, PD-1 ligands, and other features of the tumor immune microenvironment with response to anti-PD-1 therapy
Janis M. Taube,Alison P. Klein,Julie R. Brahmer,Haiying Xu,Xiaoyu Pan,Jung H. Kim,Lieping Chen,Drew M. Pardoll,Suzanne L. Topalian,Robert A. Anders +9 more
TL;DR: Tumor PD-L1 expression reflects an immune-active microenvironment and, while associated other immunosuppressive molecules, including PD-1 andPD-L2, is the single factor most closely correlated with response to anti–PD-1 blockade.
Journal ArticleDOI
Inhibitory B7-family molecules in the tumour microenvironment
Weiping Zou,Lieping Chen +1 more
TL;DR: The roles of these B7 molecules in the dynamic interactions between tumours and the host immune system, including their expression, regulation and function in the tumour microenvironment are focused on.
Journal ArticleDOI
Classifying Cancers Based on T-cell Infiltration and PD-L1
Michele W.L. Teng,Michele W.L. Teng,Shin Foong Ngiow,Antoni Ribas,Mark J. Smyth,Mark J. Smyth +5 more
TL;DR: It is proposed that four different types of tumor microenvironment exist based on the presence or absence of tumor-infiltrating lymphocytes and programmed death-ligand 1 (PD-L1) expression, and this stratification is reviewed.